title: The P. furiosus mre11/rad50 complex promotes 5' strand resection at a DNA double-strand break.
abstract: The Mre11/Rad50 complex has been implicated in the early steps of DNA double-strand break (DSB) repair through homologous recombination in several organisms. However, the enzymatic properties of this complex are incompatible with the generation of 3' single-stranded DNA for recombinase loading and strand exchange. In thermophilic archaea, the Mre11 and Rad50 genes cluster in an operon with genes encoding a helicase, HerA, and a 5' to 3' exonuclease, NurA, suggesting a common function. Here we show that purified Mre11 and Rad50 from Pyrococcus furiosus act cooperatively with HerA and NurA to resect the 5' strand at a DNA end under physiological conditions in vitro. The 3' single-stranded DNA generated by these enzymes can be utilized by the archaeal RecA homolog RadA to catalyze strand exchange. This work elucidates how the conserved Mre11/Rad50 complex promotes DNA end resection in archaea and may serve as a model for DSB processing in eukaryotes.
authors.affiliation: The Howard Hughes Medical Institute, Department of Molecular Genetics and Microbiology, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Ben B
authors.initials: BB
authors.lastname: Hopkins
authors.forename: Tanya T
authors.initials: TT
authors.lastname: Paull
mesh_terms: D019843:Archaeal Proteins / Q000302:isolation & purification / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004706:Endodeoxyribonucleases / Q000302:isolation & purification / Q000378:metabolism*; D005090:Exodeoxyribonucleases / Q000302:isolation & purification / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000302:isolation & purification / Q000378:metabolism; D025941:Protein Interaction Mapping; D020027:Pyrococcus furiosus / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*
chemical_list: D019843:Archaeal Proteins; D009097:Multienzyme Complexes; D004247:DNA; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; C415985:Mre11 protein, archaeal; C415984:Rad50 protein, archaeal